Linked Life Data

14966375

Source:http://linkedlifedata.com/resource/pubmed/id/14966375

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-17
pubmed:abstractText
Vascular endothelial growth factor C (VEGF-C) is an important growth factor that governs lymphatic spread and the development of intraperitoneal tumors associated with epithelial ovarian cancer; however, its regulation is not yet understood. Overexpression of Her-2/NEU is related to poor survival in advanced epithelial ovarian carcinoma patients. Accordingly, this study attempted to analyze the association between the Her-2/NEU oncogene and VEGF-C in ovarian carcinoma and to elucidate the molecular mechanism of VEGF-C induction by Her-2/NEU. Immunohistochemistry was used to determine the expression of Her-2/NEU and VEGF-C in tissues from 41 patients with epithelial ovarian carcinoma. Several Her-2/NEU-stably-transfected Caov-3 ovarian carcinoma cells were used to evaluate the effect of Her-2/NEU on VEGF-C, the possible regulation mechanism, and the biological function of VEGF-C. Our experimental results identified a significant association between the Her-2/NEU oncogene and VEGF-C expression in both epithelial ovarian cancer patients (p < 0.05; Fisher's exact test) and in vitro cell lines. The overexpression of Her-2/NEU in Caov-3 ovarian cancer cells resulted in induction of a considerable amount of VEGF-C mRNA and protein; this process was dose-dependently inhibited by herceptin. The generation of VEGF-C significantly increased endothelial permeability. Pharmacological and genetic inhibition assays revealed that the cytoplasmic signaling molecule, p38 MAPK, and the transcriptional factor, NF-kappa B, are critically involved in the transcriptional activation of the VEGF-C gene by Her-2/NEU. In conclusion, this work clearly establishes that the Her-2/NEU oncogene is essential for the regulation of VEGF-C in ovarian carcinoma. It may be possible to use the monoclonal antibody targeting Her-2/NEU receptor to limit the formation of malignant ascites and lymphatic spread in ovarian carcinoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1021-7770
pubmed:author
pubmed:copyrightInfo
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-59
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14966375-Ascites, pubmed-meshheading:14966375-Capillary Permeability, pubmed-meshheading:14966375-Cell Line, Tumor, pubmed-meshheading:14966375-Cells, Cultured, pubmed-meshheading:14966375-Coculture Techniques, pubmed-meshheading:14966375-Endothelium, Vascular, pubmed-meshheading:14966375-Female, pubmed-meshheading:14966375-Gene Expression Regulation, Neoplastic, pubmed-meshheading:14966375-Humans, pubmed-meshheading:14966375-Lymphangiogenesis, pubmed-meshheading:14966375-Mitogen-Activated Protein Kinases, pubmed-meshheading:14966375-NF-kappa B, pubmed-meshheading:14966375-Neoplasm Invasiveness, pubmed-meshheading:14966375-Ovarian Neoplasms, pubmed-meshheading:14966375-Receptor, erbB-2, pubmed-meshheading:14966375-Signal Transduction, pubmed-meshheading:14966375-Transcription, Genetic, pubmed-meshheading:14966375-Transfection, pubmed-meshheading:14966375-Umbilical Veins, pubmed-meshheading:14966375-Vascular Endothelial Growth Factor C, pubmed-meshheading:14966375-p38 Mitogen-Activated Protein Kinases
pubmed:articleTitle
Overexpression of Her-2/NEU in epithelial ovarian carcinoma induces vascular endothelial growth factor C by activating NF-kappa B: implications for malignant ascites formation and tumor lymphangiogenesis.
pubmed:affiliation
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't